scholarly journals Nonalcoholic Fatty Liver Disease (NAFLD): Pathogenesis and Noninvasive Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 15
Author(s):  
Vicneswarry Dorairaj ◽  
Siti Aishah Sulaiman ◽  
Nadiah Abu ◽  
Nor Azian Abdul Murad

The global prevalence of nonalcoholic fatty liver disease (NAFLD) or metabolic associated fatty liver disease (MAFLD), as it is now known, has gradually increased. NAFLD is a disease with a spectrum of stages ranging from simple fatty liver (steatosis) to a severe form of steatosis, nonalcoholic steatohepatitis (NASH), which could progress to irreversible liver injury (fibrosis) and organ failure, and in some cases hepatocellular carcinoma (HCC). Although a liver biopsy remains the gold standard for accurate detection of this condition, it is unsuitable for clinical screening due to a higher risk of death. There is thus an increased need to find alternative techniques or tools for accurate diagnosis. Early detection for NASH matters for patients because NASH is the marker for severe disease progression. This review summarizes the current noninvasive tools for NAFLD diagnosis and their performance. We also discussed potential and newer alternative tools for diagnosing NAFLD.

Author(s):  
Søren Møller ◽  
Nina Kimer ◽  
Thit Kronborg ◽  
Josephine Grandt ◽  
Jens Dahlgaard Hove ◽  
...  

AbstractNonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.


2021 ◽  
Vol 22 (18) ◽  
pp. 9969
Author(s):  
Mariano Schiffrin ◽  
Carine Winkler ◽  
Laure Quignodon ◽  
Aurélien Naldi ◽  
Martin Trötzmüller ◽  
...  

Men with nonalcoholic fatty liver disease (NAFLD) are more exposed to nonalcoholic steatohepatitis (NASH) and liver fibrosis than women. However, the underlying molecular mechanisms of NALFD sex dimorphism are unclear. We combined gene expression, histological and lipidomic analyses to systematically compare male and female liver steatosis. We characterized hepatosteatosis in three independent mouse models of NAFLD, ob/ob and lipodystrophic fat-specific (PpargFΔ/Δ) and whole-body PPARγ-null (PpargΔ/Δ) mice. We identified a clear sex dimorphism occurring only in PpargΔ/Δ mice, with females showing macro- and microvesicular hepatosteatosis throughout their entire life, while males had fewer lipid droplets starting from 20 weeks. This sex dimorphism in hepatosteatosis was lost in gonadectomized PpargΔ/Δ mice. Lipidomics revealed hepatic accumulation of short and highly saturated TGs in females, while TGs were enriched in long and unsaturated hydrocarbon chains in males. Strikingly, sex-biased genes were particularly perturbed in both sexes, affecting lipid metabolism, drug metabolism, inflammatory and cellular stress response pathways. Most importantly, we found that the expression of key sex-biased genes was severely affected in all the NAFLD models we tested. Thus, hepatosteatosis strongly affects hepatic sex-biased gene expression. With NAFLD increasing in prevalence, this emphasizes the urgent need to specifically address the consequences of this deregulation in humans.


2016 ◽  
Vol 36 (4) ◽  
pp. 427-432 ◽  
Author(s):  
Ivana Mikolasevic ◽  
Sandra Milic ◽  
Sanjin Racki ◽  
Luka Zaputovic ◽  
Davor Stimac ◽  
...  

BackgroundRecent investigations indicated that nonalcoholic fatty liver disease (NAFLD), a hepatic component of metabolic syndrome (MS), is associated with an increased risk of cardiovascular disease (CVD). Accordingly, we were interested in exploring the frequency of NAFLD in peritoneal dialysis (PD) patients and analyzing factors in PD patients associated with NAFLD occurrence. In addition, we were interested in investigating whether NAFLD is associated with higher CVD risk in our PD patients.MethodsIn the present cross-sectional study, we analyzed 58 PD patients. The controlled attenuation parameter (CAP) was used to detect and quantify liver steatosis with the help of transient elastography (TE) (FibroScan, Echosense SA, Paris, France). A carotid ultrasound was performed in all patients to measure carotid intimae media thickness (IMT) and plaque as surrogate measures of increased CVD risk, and we investigated their association with NAFLD.ResultsNonalcoholic fatty liver disease was present in 74.1% of PD patients. Peritoneal dialysis/nonalcoholic fatty liver disease patients had statistically greater daily (136.5 ± 62.6 vs 93.6 ± 36.1; p = 0.02) and monthly (4,095.3 ± 1,877.7 vs 2,806.6 ± 1,083.2; p = 0.02) glucose load in comparison to the non-NAFLD/PD patients. In the next step, we were interested in analyzing what demographic and clinical characteristics in our PD patients are associated with a higher NAFLD occurrence. Presence of diabetes mellitus (DM), arterial hypertension (AH), dyslipidemia, body mass index > 25 kg/m2, and daily glucose load > 100 g were associated with NAFLD occurrence. Peritoneal dialysis patients with NAFLD showed more carotid atherosclerosis than PD patients without NAFLD. In addition, CAP values (as indicator of liver steatosis) showed strong positive association with IMT (r = 0.801; p < 0.0001). Nonalcoholic fatty liver disease was a strong predictor of carotid atherosclerosis in PD patients.ConclusionNonalcoholic fatty liver disease is highly prevalent in PD patients. Peritoneal dialysis patients with NAFLD are at high risk of atherosclerosis. Assessment of NAFLD in PD patients may be helpful for CVD risk stratification.


Author(s):  
Marta Flisiak-Jackiewicz ◽  
Anna Bobrus-Chociej ◽  
Natalia Wasilewska ◽  
Dariusz Lebensztejn

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which predispose to more serious hepatic conditions. It ranges from simple liver steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis and even end-stage liver disease. Since obesity became one of the most important health concerns wordwide, a considerable increase in the prevalance of NAFLD and other metabolic implications has been observed, both in adults, and children. Due to the coexistence of visceral obesity, insulin resistance, dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome (MetS). These relationship between NAFLD and MetS led to set up in adults new term combining both of these conditions, called metabolic dysfunction-associated fatty liver disease (MAFLD). Based of these findings, we propose set of criteria, which may be useful to diagnose MAFLD in children and adolescents.


2015 ◽  
Vol 53 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Ionel Copaci ◽  
Ioana Lupescu ◽  
Elena Caceaune ◽  
Grethi Chiriac ◽  
G. Ismail

Abstract Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance and metabolic syndrome, which are linked to obesity. The aim of the study was to assess if weight reduction through 12 months of lifestyle intervention and exercise would lead to improvement of steatosis. Methods. In a prospective observational study 86 overweight subjects (51 men, 35 women) with steatosis were recruited, after excluding other etiologies. Patients were assigned a caloric goal and a daily fat goal. Physical activity focused on moderate-intensity activities. Blood samples (biochemistry, HOMA-IR, cytokine levels, steatotest) were collected at entry and months 6 and 12. All subjects underwent abdominal CT scan before commencement and after 12 months to assess visceral and subcutaneous adipose tissue (VAT/SAT) area. Results. After 12 months baseline descriptive characteristics (weight, BMI, waist circumference) decreased significantly. Biochemical parameters that decreased significantly were: GGT (40.0 ± 18.0 vs 31.1 ± 13; p = 0.01), ALT (58.5 ± 23.5 vs 32,7 ± 14.8; p = 0.001), cholesterol (236.4 ± 54.8 vs 204.8 ± 91; p = 0.05), LDL (160.1 ± 47.4 vs 125.3 ± 40; p = 0.05) and HOMA-R (4.86 ± 0.63 vs 3 ± 0.41; p = 0.018). Steatotest improved significantly (0.68 ± 0.16 vs 0.38 ± 0.14; p = 0.02). Modification of adipocytokines was significant for leptin (p = 0.018) and adiponectin (p = 0.003). Factors associated with regression of steatosis were weight, BMI, ALT, waist circumference, GGT, HOMA, leptin, VAT and steatotest. Multivariate logistic regression showed the following factors related to improved steatosis: BMI < 25 kg/m2, ALT < 42 U/L, leptin < 10.5 ng/ml and adiponectin > 8.4 μg/ml. Conclusions. Overweight persons who achieve significant reductions in body weight through 12 months of physical activity and low caloric diet can decrease liver fat, VAT and SAT. Even in those with minimal weight loss ALT levels, steatosis, adipokines and cardiovascular risk factors improved.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Tamara Milovanovic Alempijevic ◽  
Milica Stojkovic Lalosevic ◽  
Igor Dumic ◽  
Nevena Jocic ◽  
Aleksandra Pavlovic Markovic ◽  
...  

Objective. Keeping in mind the rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the need to establish noninvasive tests for its detection, the aim of our study was to investigate whether platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) can predict the presence of liver fibrosis in this group of patients. Methods. In 98 patients with NAFLD and 60 healthy volunteers, complete blood counts with automated differential counts were performed and values of PC, PDW, MPV, and PCT were analyzed. Results. Patients with NAFLD had lower PC and higher MPV, PCT, and PDW compared to the controls (P < 0.05). When NAFLD group was stratified according to severity of liver fibrosis, there was a statistically significant difference in the average values of PDW and PC between the groups (P < 0.05). Conclusion. Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when compared to the healthy controls. Further studies are needed to establish their potential use for prediction of the degree of liver steatosis and fibrosis in NAFLD patients.


2018 ◽  
Vol 12 (3) ◽  
pp. 639-648 ◽  
Author(s):  
Uriel A. López-Lemus ◽  
Raquel Garza-Guajardo ◽  
Oralia Barboza-Quintana ◽  
Alejandrina Rodríguez-Hernandez ◽  
Alejandro García-Rivera ◽  
...  

Metabolic syndrome (MS) has been associated with testicular damage. Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease that affects different organs, but its effect on the testes is unknown. A study analyzing germ cell involvement on BALB/c mice was carried out. A parallel comparative study was conducted that investigated alterations in the germinal epithelium of male humans that died from an unrelated acute event. The complete medical histories and histologic samples of the thoracic aorta, liver tissue, and testicular tissue from the deceased subjects were collected. The degree of germinal epithelial loss (DGEL) was evaluated and the clinical and histologic data were compared between individuals with and without NAFLD. The only metabolic or morphologic variable that caused a significant difference in the DGEL, in both the animal model and humans, was the presence of liver steatosis. The percentage of steatosis was also correlated with the percentage of the DGEL. In humans, steatosis (greater than 20%) increased the risk 12-fold for presenting with a severe DGEL (OR: 12.5; 95% CI [1.2, 128.9]; p = .03). There was no association with age above 50 years or MS components. Steatosis grade was also correlated with atherosclerosis grade. NAFLD was a strongly associated factor implicated in severe DGEL, as well as the testis was identified as a probable target organ for damage caused by the disease. This finding could result in the search for new approach strategies in the management of men with fertility problems. Further studies are required to confirm these results.


2019 ◽  
Vol 97 (1) ◽  
pp. 23-36 ◽  
Author(s):  
Selene de Jesús Acosta-Cota ◽  
Elsa Maribel Aguilar-Medina ◽  
Rosalio Ramos-Payán ◽  
Ana Karen Ruiz-Quiñónez ◽  
José Geovanni Romero-Quintana ◽  
...  

The high intake of sweetened drinks is associated with obesity and insulin resistance. These pathologies are directly related to the development of nonalcoholic fatty liver disease (NAFLD), considered a condition of metabolic syndrome (MS). Due to their increasing worldwide prevalence, experimental animal models have been developed to gain a better understanding of its physiopathology; notwithstanding, few studies have evaluated its progression in association with MS and ingestion of sweetened drinks. Therefore, the aim of this study was to understand the pathophysiologic characteristics of NAFLD related to sucrose concentration and time of ingestion in rats. Wistar rats were divided into 2 groups with free access to either tap water or 30% sucrose, and euthanized at 12, 16, or 20 weeks; and 2 additional groups were given free access to either 40% or 50% sucrose and were euthanized at 20 weeks. Biochemical parameters and levels of serum cytokines were measured, and histology was performed. Ingestion of 30% sucrose induced liver steatosis until 16 weeks (grade 2) and 20 weeks (grade 3). Meanwhile, during 20 weeks, 40% sucrose induced grade 5 of nonalcoholic steatohepatitis (NASH) and 50% sucrose induced grade 6 of NASH and fibrosis. This study demonstrated that increasing time of induction and concentration of sucrose ingestion resulted in a higher grade of NAFLD.


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